Seminar Title: "Photodynamic Therapy, Toils and Troubles: Problems Solved with Tiny Bubbles.”
ABSTRACT: Photodynamic therapy (PDT) uses visible light, a sensitizer such as a porphyrin, and oxygen gas to create singlet oxygen (1O2), a reactive oxygen species that can kill cancer cells. Historically, PDT has remained a non-invasive treatment, using red light and ambient oxygen after intravenous administration of the sensitizer. Here we describe an invasive methodology for PDT that uses highly efficient blue light coupled with localized microbubble-based delivery of sensitizer and oxygen. Lipid-based air bubbles with stabilizers are administered via a teflon or stainless steel catheter containing a concentrically placed fiber-optic cable. Ultrasound transducers are used to acoustically image the catheter and bubbles. Ultrasound can also be used to manipulate the bubbles (moving or popping). The kinetics and topology of singlet oxygen production can be studied quantitatively by reacting secondary amines with the 1O2 to produce stable nitroxide radicals, detectable at μM concentrations by electron paramagnetic resonance (EPR) spectroscopy.1 The sensitivity of nitroxide EPR spectra to local order in heterogeneous structures such as bubbles, vesicles, and micelles will also be presented and discussed.
1Zigler, et al., Photochem. Photobiol. Sci. 2014, 13, 1804–1811.
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Professor Forbes' research interests span a wide area of physical organic chemistry. His primary focus is studying free radical structure, dynamics and reactivity using a variety of magnetic resonance techniques. Current projects include the fundamentals of ‘‘spin chemistry,’’ proton-coupled electron transfer reactions, singlet oxygen topology in heterogeneous media, drying and curing processes in thin films and coatings, and the photodegradation and chain dynamics of polymers. Malcolm has published more than 110 papers and book chapters, and has presented more than 160 invited lectures.

Fri, Sep 23, 2016

Md Bhuiyan. Seminar Title: “Making Discrete, Self-Assembling Naphthalenediimide Nanotubes”
Abstract
In 2007, the Sanders group at the University of Cambridge reported the serendipitous discovery of α-amino acid functionalized naphthalenediimides (NDIs) forming a dynamic combinatorial library (DCL) in chloroform where NDIs self-assemble into helical nanotubes. Held together by intermolecular hydrogen bonds, these structures exist in dynamic equilibrium as the terminal NDIs regularly disassociate from the nanotube while free NDIs [re]associate. Three NDI subunits complete one turn of the nanotubes such that every i and i+3 NDIs are coplanar. Horizontal hydrogen bonds form between adjacent carboxylic acids of NDIs i and i+1. Interestingly, weaker diagonal hydrogen bonds also form between the aromatic naphthyl core hydrogens and imide carbonyls of NDIs i and i+3. L,L-amino acid functionalized NDIs form left handed helices while their D,D-counterparts form right handed helices. The NDIs are readily synthesized via reaction of naphthalene dianhydride (NDA) and the amino acid(s) of interest under microwave irradiation. The self-assembly of helical supramolecular structures is generally realized through a cooperative binding mechanism because of the increase in number of interactions between subunits upon completion of the first turn. Unexpectedly, the Sanders nanotubes were found to assemble via a noncooperative, isodesmic process because of enthalpy-entropy compensation effects. The nanotubes also display a wealth of intriguing host-guest chemistry, having shown the ability to complex C60, ion-pairs, and extended aromatic molecules. The preparation of self-assembling nanostructures of discrete size is a current challenge in the field of supramolecular chemistry. In chlorinated aprotic solvents, NDIs self-assemble uncontrollably, forming nanotubes of varying length. Molecular modeling studies done by the Hansen group suggest that making a single substitution into the aromatic naphthalene core of NDIs would limit the size of the nanotubes to a two-turn helix as the bulkier substituents could sterically prevent further assembly at the bases of the nanotubes. Because existing halogenating reactions of NDA give a mixture of difficult-to-separate mono-, di-, tri-, and tetra- substituted NDAs, the Hansen group attempted to nitrate NDA via electrophilic aromatic substitution (EAS) chemistry. While initial attempts using sulfuric and nitric acid failed, even more vigorous conditions employing superacids developed by George Olah were successful. The monosubstituted nitro NDA required further modification before being functionalized by amino acids to eliminate the possibility of nucleophilic aromatic substitution (NAS) chemistry at the nitro position, and to ensure successful imide condensation. Following reduction of the nitro group, and its subsequent acetylation, the monosubstituted N-acetyl bis-trityl cysteine NDI was successfully synthesized via microwave chemistry. Determination of nanotube formation and further investigations will be done using variable temperature CD and 1H NMR spectroscopy in the coming weeks. If we are successful in controlling the size of the naphthalene diimide nanotubes, we would like to characterize their thermodynamic properties, further explore their host-guest chemistry, assemble them in protic solvents, and investigate the relationship between their aromatic core electronic structures and nanotube formation.

Adrian Chan. Seminar Title: “Allosteric Activation of Engineered Protein Tyrosine Phosphatases by Biarsenical Small Molecules”
Abstract
Protein Tyrosine Phosphatases (PTPs) are important components in cellular signaling pathways. In 2015, the Bishop Lab developed a mutant form of PTP1B that can be activated upon incubation with biarsenical small molecules. The mutant had three cysteine point mutations at positions 184, 186, and 187 in the highly conserved WPD loop, and is hence called 3C-PTP1B. The thesis 's aim is threefold: (1) to test the generalizability of Knowlton’s approach, (2) to identify any potential problems in applying this activation strategy in a cell-signaling study, and (3) to identify any patterns present in the biarsencial-mediated activation of each of these mutants. If proven generalizable, this activation strategy can be used in cell-signaling studies to investigate the in vivo substrate specificities and physiological function of different PTPs.

Jesse Fajnzylber. Seminar Title: “Targeting a Cryptic Allosteric Site for Selective Inhibition of Shp2”
Abstract
The protein tyrosine phosphatases (PTPs) are a family of cell-signaling enzymes that dephosphorylate phosphotyrosine in protein substrates. Proper regulation is essential to maintaining homeostasis in human cells and misregulation of this family is associated with many human diseases. One PTP, Shp2, has been linked to many cancers when it is hyperactive. Therefore finding a molecule that could selectively inhibit Shp2 could have therapeutic effects. It is, however difficult to inhibit a specific PTP due to similarities of active sites within the family, and therefore targeting a unique PTP with active-site directed inhibitors is immensely difficult. Furthermore, because PTP active sites bind to negatively charged phosphotyrosine-containing substrates, drug-like compounds that would effectively mimic a phosphotyrosine are often negatively charged and therefore are not cell-permeable. An alternative approach to inhibition is binding to an allosteric site, which would allow the substrate to be bioavailable and also specific to a single PTP. Recently, the Bishop lab discovered that the molecule FlAsH binds well to Shp2. Upon further investigation, it was established that FlAsH binds to an allosteric site that is unique to this specific protein. FlAsH itself cannot be used pharmaceutically because it contains arsenic, which is toxic, and it also binds to many other proteins outside of the PTP family; however, it provided a realistic non-toxic method for Shp2 inhibition. The goal of my work in the summer of 2015 was to establish a library of small drug-like compounds that could potentially bind to the allosteric site that was previously discovered. Of the library, one of compounds seems to have moderate success with uniquely inhibiting Shp2. Going forward, I will synthesize derivatives of this molecule in the hopes of finding a more potent Shp2-unique inhibitor.

Fri, Sep 30, 2016

Eric Conklin. Seminar Title: "Supramolecular Assembly of Donor-Acceptor Energy Transfer System."
Abstract: A supramolecular complex in a collection of two or more molecules held together by noncovalent forces. Supramolecular assembly of model systems enables researchers to control an interaction of interest in order to shed light on an unfamiliar pathway or process. For example, supramolecular chemists are gaining new insight on Alzheimer’s disease by imposing small chemical modifications to synthetic model systems of fibrillar structures that inhibit or limit the molecular aggregation. In our study of supramolecular assembly, a hydrogen-bonded (--[H]--) model system for energy transfer was created using a porphyrinoid derivative, phlorin, and a carboxylate-appended BODIPY moiety. The phlorin is hydrogen bonded to the BODIPY-carboxylate through the axial position, thus changing the electronic structure of the phlorin moiety as evidenced by changes in the UV-visible absorption spectrum. Using transient absorption and time-resolved photoluminescence techniques, the lifetime of the excited-state for both BODIPY-carboxylate, the energy transfer donor, and the BODIPY-carboxylate--[H]--phlorin complex, the energy transfer donor and acceptor, were measured. Binding of the phlorin to the BODIPY-carboxylate, shortened the excited state lifetime of the BODIPY-carboxylate moiety. The lifetimes were used to yield a quenching rate of 1.52*10-10 s-1. The use of supramolecular assembly to control energy transfer will pave the way to creating model systems that undergo electron transfer through the axial position of the phlorin, and the donor-acceptor interactions can be opened up to studies of proton-coupled electron transfer.

Samantha Nyovanie. Seminar Title: Synthesis of Organosiloxanes and Organoclays for Polymer-Clay Nanocomposites (PCNs)"
Abstract: Polymer–clay nanocomposites (PCNs) have been a growing field of interest and research since the discovery that the presence of clay (at less than 5 wt%) can improve the mechanical, barrier, flame retardant, electrical, and biodegradable properties of the polymer. The synthesis of these nanocomposites is challenging due to the potential incompatibility of the inorganic clay and organic polymer components, due to their different chemical compositions and properties. The Burkett lab has devised a synthetic technique that enables the polymer chains to be end-tethered onto the surfaces of the clay layers, creating a polymer brush structure. This technique involves functionalizing an existing clay with a polymerization reaction initiator, such as a hydroxymethyl group, and inducing polymerization from those sites, creating polymer brush PCNs. This thesis develops a different approach for preparing initiator-functionalized clays: first functionalizing a commercial organosiloxane, 3 aminopropyltriethoxysilane, with an initiator-containing group, 5 (hydroxymethyl)salicylaldehyde, and then using this new organosiloxane for the synthesis of the clay. This method provides good control of the composition of the clay, and it facilitates the synthesis of clays with mixtures of functional groups, such as 5 (hydroxymethyl)salicylideneimine (HMS) and salicylideneimine (Sal). This research will investigate the possibility of tailoring the distribution of polymerization initiator sites: 100% HMS, 50% HMS/50% Sal, and 25% HMS/50% Sal. This strategy will create polymer brush PCNs with different polymer chain densities

Niyi Odewade. Seminar Title: "Ruthenium-Based Donor Compounds as Building Blocks in Proton Coupled Electron Transfer Model Systems."
Abstract: The rapid growth in world population will not only double global energy needs by 2050 but will also increase CO2 emission by another 50%. Consequently, there is a growing demand for carbon-neutral energy that can adequately and safely satisfy the needs of the planet. Herein lies the imperative to study proton-coupled electron transfer (PCET). PCET theory articulates a concerted transfer of protons and electrons via an overlap of donor and acceptor wave functions, which drastically decreases the activation barrier of energy-related molecules. Significantly, this process underpins the molecular chemistry of renewable energy, specifically chemical reactions that drive the capture, conversion, and storage of energy. In our work, we examine several newly synthesized ruthenium-based donor molecules - Ru(II)Cp*benzoate (Ru-Benz), Ru(II)Cp*carbamidinate (Ru-CarbAm) and Ru(II)Cp*methylcarbamidinate (Ru-MeCarbAm) and their PCET reaction with a well-studied ruthenium-based photo-oxidant, ruthenium trisbipyridine (Ru(bpy)3). Through the use of UV-visible absorption and fluorescence spectroscopy and electrochemistry, we have been able to discern early correlations between thermodynamic and kinetic properties. With further characterization, we aim to provide experimental results that can be used to further develop the PCET theory.

Megan Tracy. Seminar Title: "Determining the Structure of 2-chloro-3,3,3-Trifluoropropene and its Dimers with Argon and Hydrogen Fluoride."
Abstract: When molecules change rotational energy levels, they release or absorb energy of a specific, set amount, typically as light in the microwave region of the electromagnetic spectrum of a specific, set frequency, which is able to be predicted based on the rotational constants of the molecule, which correlate to the molecule’s structure based on its moments of inertia. The structure of 2-chloro-3,3,3-trifluoropropene was thus determined based on the assignment of the Fourier-transform microwave spectrum of the gas to the ab initio calculated rotational transition peaks based on the minimum energy structure predicted by Gaussian09. The corresponding spectra of each of the three C-13 singly-substituted isotopologues of the molecule, the Cl-37 singly substituted isotopologue, and the three doubly substituted C-13 and Cl-37 isotopologues were also assigned, with the addition of Balle-Flygare narrow band spectroscopy to measure transitions that are too weak to be obtained in the broadband spectrum, and the rotational constants calculated based on these assignments were used in Kraitchman calculations to further define the position of the different atoms within the molecule. Using this structure of the molecule, the structure and rotational constants of the minimum energy arrangement of the molecule’s dimer with argon were predicted by Gaussian09 and were used to generate a predicted spectrum, which is currently being assigned to the chirped pulse broad band spectrum of the gas. This thesis will involve studying the dimer of the molecule with HF in this manner, and future work will likely involve the other protic acids HCl and HCCH.

Fri, Oct 14, 2016

Sidney Lin. Seminar Title: "NMR Investigation of Chain Confirmation Within Polymer Brush-Clay Nanocomposite Analogues."
Abstract: Composites of inorganic and organic materials are of growing interest given their enhanced thermal and mechanical properties. Polymer-clay nanocomposites (PCNs), which are composed of organic polymers intermixed with inorganic clay, exhibit these enhanced properties even when the material is less than 10% clay by mass. If the polymer chains are end-tethered to the clay sheets, the array is referred to as a polymer brush structure. Chain crystallinity, conformation, and dynamics are key structural features of polymer brusher. However, given the challenges inherent in studying local structure within long polymers, a polymer analogue, dodecyl sulfate (SDS), on the surface of a zinc aluminum hydroxide clay will be studied. Thus it is possible to study the effect of chain packing on chain conformation and dynamics at the surface of clays. Nuclear magnetic resonance, X-ray diffraction, Thermogravimetric analysis and Infrared spectroscopy will be utilized to study the chain crystallinity, conformation, and dynamics of these PCN analogues.

Miles Wronkovich. Seminar Title: "Structure Determination of the 2,3,3,3-Tetrafluoropropene-Hydrogen Chloride Complex Through Microwave Spectroscopy.”
Abstract: With the introduction of microwave spectroscopy in physical chemistry, many small molecules and their complexes have been studied in order to determine their structures and understand the nature of van der Waals interactions. The lower energy microwave region is conducive to this type of work due to the small spacings and, therefore, narrower energy gaps between rotational energy levels. This research focuses on the complex between the molecule 2,3,3,3-tetrafluoropropene (2-TFP) and the protic acid hydrogen chloride (HCl). The structure of the 2-TFP monomer has been determined by performing ab initio calculations with Gaussian 09 to optimize the geometry and predict rotational constants for the monomer. A microwave spectrum was taken using the broadband chirped-pulse Fourier transform microwave spectrometer and, based upon the predicted constants, transitions were assigned to the experimental spectrum. In addition, spectral assignments have been completed for the three singly-substituted 13C species of the monomer. The complex of the monomer and an argon atom, an important waypoint for this work, has been studied as well. The main isotopologue of the argon complex has been assigned, however, the 13C transitions seem too weak to accurately assign and a narrowband spectrum may need to be taken. A similar process has begun for the 2-TFP-HCl complex itself as ab initio calculations are being computed. For this complex, preliminary results show the HCl prefers a nonplanar conformation with the ethyl fluorine aligned with the proton and the fluorine’s geminal hydrogen aligned with the chloride. Further calculations will be done to investigate the effect the planarity of the acid has on the energy of the previous result as well as to find other low energy configurations of the complex.

Mbatang (Desmond) Acha. Seminar Title: "Developing Chiral Tagging Molecular Rotational Spectroscopy for Assignment of Stereochemistry."
Abstract: Chiral stereoselectivity is vital to the physiological activity of biological and pharmaceutical molecules. However, existing techniques for the detection and quantification of chirality are inefficient. In 2013, Patterson, Schnell and Doyle developed an enantiomer-specific method of chiral detection by using three-wave mixing of dipole moments. The enantiomer-dependent Rabi frequency of the molecule was mapped onto the phase of emitted microwave radiation and the detected signal is at 1800 phase difference. This technique was used to distinguish between R and S enantiomers of 1,2-propanediol and can potentially extended to distinguish chirality of multiple species in a mixture. However, this method is only effective for low enantiomeric excess measurements, and significant uncertainties arise in the high enatiopurity limit (ee>99). Chiral tagging is a promising alternative method that employs chirped-pulse Fourier transform microwave (CP-FTMW) rotational spectra to determine the detailed structural orientation of chiral complexes. The central idea is that a hetero-dimer of two indistinguishable chiral species is a cluster of two homochiral (RaRa, or SaSa) or heterochiral (RaSa or SaRa) disatereomers, which have distinguishable rotational spectra. The Marshall and Leung Labs are adept at structure elucidation using microwave spectroscopy based upon a systematic study of haloethylene compounds, and we are developing a “gold standard” result for the determination of absolute configuration at high ee limits using trifluoromethyl oxirane (TFMO) as the chiral tag. Over the summer, the detailed rotational spectrum of a sample of TFMO and its 13C and 18O isotopologues (in natural abundance) was analyzed. Its main rotational constants and its geometry (bond lengths and angles between substituted atoms) were determined. The next steps are studying the structure of 2-vinyloxirane, and complexing an enantiopure sample of that molecule as a chiral tag with TFMO. The heavy atom structure of the resulting diastereomers will be determined using a Kraitchman analysis. The complex is formed through non-covalent interactions, primarily C-O∙∙∙H and C-F∙∙∙H, which cause minimal perturbation of the molecules. The diastereomers are distinguished by their rotational spectra and the absolute configuration of the chiral tag is known. Subsequently, the absolute stereochemistry of TMFO can be inferred and its absolute structure produced.

The Elliott Group has multi-disciplinary interests that span redox enzymology, electrochemistry / electrocatalysis, microbiology and the use of spectroscopy to study redox active proteins and enzymes. We study a wide range of multi-electron redox enzymes containing multiple redox cofactors, using direct electrochemistry and electrochemical methodologies to bear upon problems in mechanistic enzymology and the development of protein-based electrodes. Areas of chemistry of interest to us include: long-range electron transfer achieved by multi-heme cytochromes, multi-electron reductions of nitrite and sulfite reduction, bacterial peroxidase activities, and CO2 reduction catalyzed by metalloproteins.

Fri, Apr 7, 2017

Theses Due - No Seminar.

Wed, Apr 12, 2017

This year's Five College Lecturer will be hosted by Hampshire College. Professor Houk's expertise is in Analytical Spectroscopy and Inorganic Mass Spectrometry. He is responsible for the development and improvement of inductively coupled plasma mass spectroscopy (ICP-MS), which revolutionize the metal detection in environmental, biological, pharmaceutical matrices, and material sciences.

April 12: Hampshire College Lecture. 4:30p.m.-5:30p.m.; Adele Simmons Hall, Ruth Hammen Auditorium. (Refreshments at 4:15p.m.)
Seminar Title: "The Origins and Development of ICP-Mass Spectrometry: A 20 Year Reasearch Project in Instrumentation."
This talk is a personal trip through the author’s grad school and postdoc days, when there were no plugand-play ICP-MS instruments. The talk also describes subsequent instrumentation developments that improved the capabilities of ICP-MS, i. e., collision cells to remove polyatomic ions, and GC and LC separations to provide speciation information. Interactions with scientific users and instrument companies played a big role in these developments, as will be described.

April 13: University of Massachusetts @ Amherst Lecture. 11:30a.m.-12:30p.m.; Lederle Graduate Research Center (LGRT) Room 1634. (Refreshments at 11:00a.m.)
Seminar Title: "Mass Spectrometry from Atoms to Metabolites: Fundamentals and Applications of ICP-MS and Laser Ablation Electrospray Ionization MS."
One approach to chemical analysis by mass spectrometry (MS) is to use an ion source that converts the sample into atomic ions, i. e., ICP-MS. Basic instrumentation, capabilities and scientific uses of ICP-MS will be described, including standard applications and new ones such as a) discovery of entirely new elements, and b) large-scale screening of antibody binding in biomedical research. Areas of new research will also be discussed.
The second, more common approach is to use an ion source that produces gas-phase ions from the analytemolecules without fragmenting them. There are many such sources; our work combines two of them, laser ablation (LA) for solid sampling plus electrospray ionization (ESI) for supplemental ionization. This combination is amenable to applications that employ mass spectrometry imaging. We use this LAESI-MS method for large scale identification of metabolite compounds in plants.

April 13: Smith College Lecture. 5:00p.m.-6:00p.m. Ford Hall, Room 240. (Refreshments at 4:45p.m.)
Seminar Title: "Structural Studies of Biomolecules by Mass Spectrometry and Ion Mobility."
There are several relatively new developments in MS that allow study of the actual 3-dimensional structures of biomolecules, not just their identification based on molecular weight and fragmentation. This talk describes the use of ion mobility separations to determine ion cross-sections, combined with ion-ion reactions to manipulate their structures. Proteins are emphasized.

Abstract: Stars and planets form from the collapse of portions of dense interstellar clouds, which are large assemblies of cold gas and dust (10 K) in interstellar space. The gas-phase is mainly molecular and contains many exotic species, including radicals, unusual isomers, and anions, most of which are organic in nature. Although hydrogen is the dominant element and H2 the dominant gas-phase molecule, most organic molecules are very unsaturated and are labeled “carbon chains” by astronomers. The dust particles are covered with ices, mainly in the form of water, CO, and CO2. During the collapse, the material evolves through a number of stages starting with an isothermal era, followed by a warm-up during which the gas-phase molecular inventory changes from a mainly exotic one to one in which most organic molecules resemble standard laboratory solvents, albeit in the gas phase. Eventually a so-called protoplanetary disk is formed around the young star, and the disk can lead to the formation of planets via coagulation of the dust particles, with an initial molecular inventory at least partially determined by the chemistry that has already occurred.

Much of what we know about the physical conditions and lifetimes of the various stages of star formation derives from molecules, which, through spectroscopy and kinetic modeling, are excellent probes of sources where they exist.1 In this talk, I will discuss the types of gas-phase and solid-state processes that synthesize molecules in assorted regions of star formation, with an emphasis on exotic gas-phase reactions and the chemistry that occurs in ice mantles.